This application seeks to examine the vascular tone baroreflex as a physiological mechanism that links the vascular actions of alcohol to adaptive behavior change. Alcohol profoundly and directly influences blood vessels to negatively affect vascular reactivity in a time- and dose-dependent manner. Abnormal vascular dynamics have far-reaching consequences due in part to the vascular tone baroreflex, which uses variability in blood vessel diameter to compensate for acute shifts in blood pressure and modulate stress reactions. The vascular tone baroreflex is a closed-loop system that functions via information exchange between the autonomic and central nervous systems. Thus, it is possible to observe the interrelationship of the physiological and neurological processes that support emotional self-regulation and stress responding by directly assessing vascular tone baroreflex activity. By comparing vascular tone baroreflex sensitivity in non- drinkers, moderate drinkers, and heavy drinkers, it may also be possible to observe how alcohol disrupts these interrelated processes and instigates the cascade of self-regulatory failures that enhance risk for using alcohol to cope with emotional dysregulation. Little is known about the vascular tone baroreflex system because, until recently, non-invasive assessment of changes in beat-to-beat vascular tone in response to perturbations was not accurate. This application uses new technology and new methodologies to validly characterize basic functional properties of the vascular tone baroreflex system. Specifically, we seek to confirm the presence of resonance in the vascular tone baroreflex system in humans, identify paradigms that effectively stimulate resonance oscillations, and explore how heavy drinking and genetic background affect vascular tone baroreflex sensitivity. If successful, these innovative studies will provide a foundation for a research program that translates basic science discoveries about vascular tone baroreflex activity to develop a clinically-relevant treatment amenable to wide-scale adoption. This project builds upon the principal investigator's prior success in applying basic knowledge about the resonance frequency in the heart rate baroreflex system to develop an empirically-supported clinical biofeedback procedure that reduces the severity of the symptoms associated with asthma, major depression, fibromyalgia, neurosis, and hypertension. As a novel therapeutic target, vascular tone baroreflex retraining through biofeedback has potential relevance for intervening in heavy alcohol use aimed at modulating emotional arousal by providing a novel behavioral strategy to help reduce stress and negative mood. PUBLIC HEALTH RELEVANCE: Variability in blood vessel diameter is an essential feature of health. Like atherosclerosis (hardening of the vessel walls), which is the leading cause of death in the United State, heavy drinking leads to a loss of this variability. In this application, we will examine the vascular tone baroreflex system, which controls blood vessel diameter variability, and explore how heavy drinking affects its sensitivity. We will also explore how a person's genetic makeup can influence the functioning of this system.